Estimates of Racial Diversity of National (USA) glucose-6-phosphate Dehydrogenase Deficiency (G6PDd) Prevalence Among Newborns

Background: Glucose-6-Phosphate Dehydrogenase deficiency (G6PDd) is the most common inherited enzyme deficiency disorder worldwide and a major risk factor for development of severe hyperbilirubinemia. Racial diversity of phenotypes and genotypes in affected individuals is likely in USA because of changing population demographics. The aim of present study was to predict an empirically estimated annual prevalence of G6PDd in newborns adjusted for geography ( State of birth), maternal racial identity and gender.

Methods: Birth statistics (2019) from National Center for Vital Statistics and CDC-WONDER data and prevalence of Races in USA were evaluated from published sources. We developed Simpsons diversity index (DI) for each State and correlated these to rates of G6PDd. Descriptive statistics describe modelled prevalence and its association with DI was assessed using Spearman Rho correlation test. We modelled State-specific incidences for six states (CA,DC,IL,MA,NY,PA] using population level allele frequencies and Race, based on Hardy–Weinberg equilibrium.

Results: We estimate 78,010 (95% CI: 76,768, 79,252) newborns had G6PDd at birth in 2019 with cumulative incidence of 20 per 1000 live births for USA. A strong association was noted for DI and prevalence proportion of G6PDd (rs- 0.5766; p<.00005). States with highest projected G6PDd incidence included DC, MS, LA, GA, MD, with ranges from 35- 48 per 1000 live births. Probability of G6PDd for female heterozygotes, based on male prevalence, ranged from 1.1- 7.5% for each racial cohort in the select six States.

Conclusion: States with diverse populations have higher rates of G6PDd (incidence range: 5 to 48 per 1000 live births. This incidence exceeds several-fold for disorders screened by state mandated newborn screening panels. These discrepancies are further confounded by known risk of severe neonatal hyperbilirubinemia that results with G6PDd and life-long risk of hemolysis. Combined universal newborn pre-discharge screening for G6PDd and bilirubin could alert and guide a clinician’s practices for parental education and closer medical surveillance during the vulnerable neonatal life.